A. Duek, L. Shvidel, A. Braester and A. Berrebi
Background: Autoimmune disorders often develop during the course of B chronic lymphocytic leukemia. The source of the autoantibodies is still uncertain: either uncontrolled production of the malignant B cells or disturbances of the residual normal B and T cells involved in the immune system.
Objectives: To evaluate immunologic parameters in B-CLL[1] associated with autoimmune disorders. As a hypothesis we postulated that in those cases, the malignant B cells might disclose an activated phenotype pattern leading to the production of autoantibodies.
Methods: In the Registry of the Israel Study Group on CLL that includes 964 patients, we found 115 cases showing a single or a complex of autoimmune disorders. We evaluated the lymphocyte morphology, immunoglobulin G and beta-2-microglobulin serum levels and positivity of the CD38 and FMC7 markers, and compared these values with those of a matched CLL population without autoimmune disorder.
Results: The main autoimmune disorders encountered were autoimmune hemolytic anemia (55 patients), Evan's syndrome (n=7), Hashimoto's thyroiditis (n=15), vasculitis (n=5) and rheumatoid arthritis (n=4). We found atypical prolymphocytic morphology in 22%, high expression of the activation antigens CD38 and/or FMC7 in 30%, and high level of immunoglobulin G (> 1000 mg/dl) and beta-2-microglobulin in 57% and 78% respectively. When compared with a matched CLL population without an autoimmune disorder, these values were statistically significant.
Conclusions: Our data, which show activated lymphocyte morphology, high levels of IgG[2] and beta-2-microglobulin, and increased expression of CD38 and/or FMC7 in a significant number of cases, suggest that some degree of activation of B cells may lead to the occurrence of an autoimmune disorder in CLL.
O. Bairey, R. Ruchlemer and O. Shpilberg
Background: Non-Hodgkin’s lymphoma of the colon is a rare and consequently poorly studied extranodal lymphoma. Most of the previous publications used old pathologic classifications and old diagnostic and treatment approaches.
Objective: To examine the clinical presentation, pathologic classification, treatment and outcome of patients with NHL[1] of the colon.
Methods: A retrospective study was performed of all patients with NHL and involvement of the colon in two medical centers. The patient group consisted of 17 patients over a 13 year period.
Results: Fourteen patients had primary involvement and 3 secondary. The ileocecal region and cecum were the most frequent sites of involvement, occurring in 76% of patients. Most patients had bulky disease: three had a diameter > 5 cm and eight a diameter > 10 cm. Aggressive histology was found in 12 patients: diffuse large B cell lymphoma in 11 and peripheral T cell lymphoma in 1. Three patients had mantle cell lymphoma and two had indolent lymphomas: mucosa-associated lymphoid tissue (n=1) and small lymphocytic (n=1). Eleven patients underwent hemicolectomy: right sided in 9 and left sided in 2, and 5 DLBCL[2] patients required emergency surgery for intestinal perforation. The median overall survival was 44 months (range 1–147). Disease stage influenced prognosis; six of seven patients with limited-stage DLBCL who received aggressive chemotherapy achieved complete remission and enjoyed prolonged survival, whereas patients with aggressive disseminated disease had resistant disease and poor survival (median 8 months).
Conclusions: Most colonic lymphomas are aggressive B cell lymphomas. Diagnosis is often delayed. Early diagnosis may prevent perforation. Those with limited-stage disease when treated with aggressive chemotherapy may enjoy prolonged survival.
The role of elective hemicolectomy to prevent perforation should be examined in prospective trials.
[1] NHL = non-Hodgkin's lymphoma
[2] DLBCL = diffuse large B cell lymphoma
M.H. Ellis, O. Ashur-Fabian, L. Trakhtenbrot and N. Amariglio
R. Gurion, D. Groshar, A. Schindel, O. Shpilberg and P. Raanani
A. Elis, J. Radnay, H. Shapiro, D. Itzhaky, Y. Manor and M. Lishner
Background: Monoclonal gammopathy of undetermined significance is defined by the presence of: low serum and/or urine monoclonal protein level; less than 10% plasma cells in bone marrow; normal serum calcium, creatinine and hemoglobin levels; and no bone lesions on full skeletal X-ray survey.
Objectives: To study the necessity of bone marrow examination for the diagnosis and clinical course of MGUS[1].
Methods: We retrospectively screened the medical records of all patients in whom monoclonal protein was found in the serum during 2001–2002 in the medical laboratories of Sapir Medical Center. Asymptomatic patients who had serum monoclonal immunoglobulin G < 3.0 g/dl or IgA[2] < 2.0 g/dl or IgM < 1.0 g/dl without anemia, renal failure, hypercalcemia or any bone lesions on skeletal survey were eligible. Full records of patients who were evaluated in the hematology clinic were available (group 1). The remaining patients were followed by their family physicians; thus we had access only to their electronic files including laboratory results and new diagnoses (group 2). Demographic and clinical parameters as well as clinical course were evaluated.
Results: Both groups (57 and 255 patients, respectively) had similar demographic, laboratory and clinical characteristics. Bone marrow examination was performed in 30 of 57 patients (group 1): 16 were normal, 8 had an excess of normal plasma cells, and 6 had excess of pathologic plasma cells. However, only in two of the latter six could a diagnosis of multiple myeloma be established. All group 1 patients were followed for 22 ± 11 months and only two developed overt multiple myeloma. During the same period, 6 of 255 patients (group 2) were diagnosed as multiple myeloma and 3 as MGUS in other hospitals. The rest had a stable course with no change in their laboratory values.
Conclusions: Our findings suggest that bone marrow examination should not be performed routinely in patients who fulfill strict clinical and laboratory criteria of MGUS.
O. Shpilberg, I. Ben-Bassat and P. Raanani
A. Nemets, I. Isakov, M. Huerta, Y. Barshai, S. Oren and G. Lugassy
Background: Thrombosis is a major cause of morbidity and mortality in polycythemia vera. Hypercoagulability is principally due to hyperviscosity of the whole blood, an exponential function of the hematocrit. PV[1] is also associated with endothelial dysfunction that can predispose to arterial disease. Reduction of the red cell mass to a safe level by phlebotomy is the first principle of therapy in PV. This therapy may have some effect on the arterial compliance in PV patients.
Objectives: To estimate the influence of phlebotomies on large artery (C1) and small artery compliance (C2) in PV patients by using non-invasive methods.
Methods: Short-term hemodynamic effects of phlebotomy were studied by pulse wave analysis using the HDI-Pulse Wave CR2000 (Minneapolis, MN, USA) before and immediately after venesection (300–500 ml of blood). We repeated the evaluation after 1 month to measure the long-term effects.
Results: Seventeen PV patients were included in the study and 47 measurements of arterial compliance were performed: 37 for short-term effects and 10 for long-term effects. The mean large artery compliance (C1) before phlebotomy was 12.0 ml/mmHg x 10 (range 4.5–28.6), and 12.6 ml/mmHg x 10 (range 5.2–20.1) immediately after phlebotomy (NS). The mean small artery compliance (C2) before and immediately after phlebotomy were 4.4 mg/mmHg x 10 (range 1.2–14.3) and 5.5 mg/mmHg x 10 (range 1.2–15.6) respectively (delta C2–1.1, P < 0.001). No difference in these parameters could be demonstrated in the long-term arm.
Conclusions: Phlebotomy immediately improves arterial compliance in small vessels of PV patients, but this effect is short lived.
M. Tokar, D. Bobilev, S. Ariad and D.B. Geffen
Background: Disseminated intravascular coagulation associated with malignant bone marrow involvement has been described as a rare complication of gastric carcinoma and most patients die within 1–4 weeks. Effective chemotherapy of the underlying malignancy may be the only way to control acute DIC[1].
Objectives: To assess the benefit of infusional 5-fluorouracil as the primary treatment of metastatic gastric carcinoma and DIC at diagnosis.
Methods: From February 2001 to January 2005, six women (median age 48 years) with gastric carcinoma who presented with diffuse bone metastases and acute DIC were treated in our department. Diagnosis was based on primary gastric and bone marrow biopsies. DIC was confirmed by laboratory findings. Initial treatment consisted of infusional 5FU[2] 200 mg/m2/day. When the bleeding tendency stopped, cisplatin 60 mg/m2 and epirubicin 50 mg/m2 given every 3 weeks were added.
Results: Within one week of starting the treatment, the clinical and laboratory signs of acute DIC were resolved in five of six patients. Upon clinical improvement, five patients subsequently received epirubicin and cisplatin. Survival, however, was short (mean 15 weeks). All patients died with symptoms of bleeding, showing clinical and laboratory signs of DIC.
Conclusions: Based on our experience, infusional 5FU is an effective regimen with negligible myelosuppression; thus, it may be a good choice as initial therapy for this group of patients. The response induced by protracted 5FU was usually short and lasted for a few weeks only. Therefore, once DIC symptoms are controlled, the addition of newer cytotoxic drugs may be necessary to consolidate the remission.
U. Elchalal, E. Gabbay, M. Nadjari, D. Varon, O. Zelig and E. Ben-Chetrit
E.S. Kokia, R. Marom, V. Shalev, Y. Jan and J. Shemer
Background: During war the health management organizations have tremendous difficulty monitoring members' needs according to geographic spread.
Objectives: To describe how an HMO[1] used its health information technology in a way that enables its management to receive updated online information on the demands of the insured, according to their distribution throughout the country during the time of the war in Lebanon in July-August 2006.
Methods: Data were derived from the computerized medical records of Maccabi Healthcare Services – the second largest HMO in Israel, providing care to more than 1.7 million members nationwide. Data on healthcare utilization by northern members were compared to the geographic distribution of clinics.
Results: The war was characterized by the massive evacuation of citizens southwards. During this period there was an abrupt decline in the utilization of medical services by northern members in the northern region. This decline returned to normal 10 days after the ceasefire. A reciprocal increase was noted in the use of health services by citizens from the north in other regions. This increase returned to normal after the war. No such pattern was noticed during the same period in 2005.
Conclusions: Real-time surveillance of trends in consumption of health services by citizens in times of regular daily living as well as during emergencies and wars is a vital management tool for medical directors responsible for providing health services.
A. Jotkowitz, A. Porath, A. Shotan, M. Mittelman, E. Grossman, R. Zimlichman, B.S. Lewis, A. Caspi, S. Gottlieb and M. Garty, for the Steering Committee of the Israeli Heart Failure National Survey 2003
Background: Despite significant advances in the therapy of heart failure, many patients still do not receive optimal treatment.
Objectives: To document the standard of care that patients hospitalized with HF in Israel received during a 2 month period.
Methods: The Heart Failure Survey in Israel 2003 was a prospective 2 month survey of patients admitted to all 25 public hospitals in Israel with a diagnosis of HF.
Results: The mean age of the 4102 patients was 73 years and 43% were female. The use of angiotensin-converting enzyme/angiotensin receptor blockers and beta blockers both declined from NYHA class I to IV (68.8% to 50.6% for ACE-inhibitor/ARB and 64.1% to 52.9% for beta blockers, P < 0.001 for comparisons). The percentage of patients by NYHA class taking an ACE-inhibitor or ARB and a beta blocker at hospital discharge also declined from NYHA class I to IV (47.5% to 28.8%, P < 0.002 for comparisons). The strongest predictor of being discharged with an ACE-inhibitor or ARB was the use of these medications at hospital admission. Negative predictors for their usage were age, creatinine, disease severity class, and functional status.
Conclusions: Despite the dissemination of guidelines many patients did not receive optimal care for HF. Reasons for this discrepancy need to be identified and modified.
N. Hod, G. Fire, I. Cohen, M. Somekh and T. Horne
Z. Shimoni, M. Ben David and M.J. Niven